TRANSCRIPTIONAL REGULATION OF THE MYELIN PROTEOLIPID PROTEIN GENE

髓磷脂蛋白脂蛋白基因的转录调控

• 批准号: 8168092
• 负责人: BRIAN T GREUEL
• 金额: $ 9.93万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168092
• 关键词: Axon; Cell Line; Cells; Computer Retrieval of Information on Scientific Projects Database; Elements; Enhancers; Funding; Gene Expression; Genes; Genetic Enhancer Element; Grant; Institution; Introns; Link; Mammals; Mediating; Mus; Myelin Proteolipid Protein; Neuraxis; Neurons; Oligodendroglia; Regulation; Regulatory Element; Reporter Genes; Research; Research Personnel; Resources; Series; Source; Testing; Testis; Transcriptional Regulation; United States National Institutes of Health; cell type; leydig interstitial cell; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Expression of the myelin proteolipid protein (Plp) gene in mammals is intimately tied to the differentiation of oligodendrocytes and reaches a peak during the period in which these cells are actively myelinating the axons of neurons in the central nervous system. Low-level expression of the Plp gene has also been detected in several non-oligodendroglial cell types, including the Leydig cells of the testis, but the functional significance of this expression has yet to be determined. Several regulatory elements/regions, located within the first intron of the Plp gene, have been implicated in the spatial and temporal regulation of Plp gene expression. One of these elements, designated the antisilencer/enhancer (ASE), appears to mediate a dramatic upsurge in Plp gene expression in oligodendrocytes by counteracting the effects of negative regulatory elements located within the first intron. One possible explanation for the lower level of Plp expression in non-oligodendroglial cells is that the ASE is much less active in these cells and is relatively ineffective in counteracting the negative regulatory elements. To test this hypothesis, we analyzed the effects of a series of Plp intron 1 deletions on the expression of a linked reporter gene (lacZ) in a transiently transfected mouse Leydig cell line (TM3). The results of these experiments confirmed that the ASE element/region of Plp intron 1 has minimal activity in Leydig cells, while general and cell type specific negative regulatory elements within the intron are very active in repressing expression of the reporter gene. Preliminary evidence also suggests that a positive regulatory element located near the 5 end of the intron, and distinct from the ASE, may function specifically in Leydig cells. This issue will be explored in more depth by looking at the effects of additional deletions near the 5 end of the intron. (to start June 1, 2004)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哺乳动物中髓鞘蛋白脂质蛋白（Plp）基因的表达与少突胶质细胞的分化密切相关，并且在这些细胞活跃地使中枢神经系统中的神经元的轴突髓鞘化期间达到峰值。 低水平表达的Plp基因也已被检测到在几个非少突胶质细胞类型，包括睾丸间质细胞，但这种表达的功能意义还有待确定。 位于Plp基因第一内含子内的几个调控元件/区域已经涉及Plp基因表达的空间和时间调控。 这些元素之一，指定的antisilencer/增强子（ASE），似乎介导了一个戏剧性的高潮，在少突胶质细胞中的Plp基因的表达，通过抵消位于第一内含子内的负调控元件的影响。 非少突胶质细胞中Plp表达水平较低的一个可能解释是ASE在这些细胞中活性低得多，并且在抵消负调控元件方面相对无效。 为了验证这一假设，我们分析了一系列的Plp内含子1缺失的影响，在一个瞬时转染小鼠Leydig细胞系（TM 3）的报告基因（lacZ）的表达。 这些实验的结果证实了Plp内含子1的ASE元件/区域在Leydig细胞中具有最小的活性，而内含子内的一般和细胞类型特异性负调控元件在抑制报告基因的表达中非常活跃。 初步证据还表明，位于内含子5端附近的正调控元件，与ASE不同，可能在Leydig细胞中特异性地起作用。 这个问题将通过观察内含子5端附近额外缺失的影响来更深入地探讨。 (to 2004年6月1日开始）